Relation between monophasic action potential duration, ST segment elevation, and regional myocardial blood flow after coronary occlusion in the pig.

There is mounting interest in the use of the monophasic action potential for electrophysiological investigation of regional myocardial ischaemia. There is, however, no systematic study of the relation between the changes in monophasic action potential and regional myocardial blood flow. In this study monophasic action potential and, for comparison, epicardial electrograms were recorded by suction electrode at 14 selected sites on the anterior surface of the normal left ventricle of the intact pig heart in situ (n = 16). The monophasic action potential duration varied across the left ventricle; it was shortest close to the left anterior descending coronary artery, increased laterally across the left ventricle, and was longer at the apex than at the base. This variation was independent of regional myocardial blood flow (measured with radiolabelled microspheres). After coronary occlusion, in nine of these pigs monophasic action potential duration significantly decreased in proportion to the reduction in regional myocardial blood flow. The ST segment of the epicardial electrogram was elevated in relation to the reduction in regional myocardial blood flow but correlated less well. The reduction in regional myocardial blood flow of approximately 50% produced maximal ST elevation. The monophasic action potential could be recorded from some sites within the border zone for up to 5 h but could not be recorded from the centre of an ischaemic zone. With ischaemic episodes of this duration there was, however, a return to baseline of the elevated ST segment for all sites within the compromised region. Monophasic action potential duration, unlike epicardial electrogram ST elevation, discriminates between central ischaemic and non-ischaemic and ischaemic sites on either side of the zone with a reduced blood flow. The results suggest that monophasic action potential duration measured by suction electrode may be a simple and reliable index of transmural-epicardial myocardial ischaemia in experimental studies and in surgery.

Liposome accumulation in chronic ischaemia is dependent on tissue necrosis.

Liposomes accumulate is ischaemic rat intestine 24 h after mesenteric occlusion. The accumulation of liposomal components is shown to depend on necrotic or allied alterations in cell integrity/function associated with chronic ischaemia. Moreover, not all liposomal components accumulate at sites of infarction. It is concluded therefore that liposomes are likely to be of little value in the diagnosis and management of ischaemic disorders.

Myocardial liposome uptake in the early stages of myocardial infarction.

Multiply-labelled neutral or positively-charged liposomes were given iv to open-chested dogs or pigs 0.5 h or 5 h after coronary artery occlusion. Myocardial blood flow was measured by labelled microspheres. Animals were killed 3.5 h or 6 h after coronary artery occlusion and the myocardial distribution of liposomal labels was correlated with that of the microspheres. No evidence was found that liposomes are taken up preferentially by ischaemic myocardium. The results suggest that liposomes have limited potential as a means of drug delivery in myocardial infarction.

Inosine as a selective inotropic agent on ischaemic myocardium?

Intravenous infusion of inosine (15 mg.kg-1.min-1) to the open-chested pig resulted in hypotension, coronary vasodilatation and slightly increased myocardial contractility. Following coronary occlusion, the action of inosine to increase myocardial contractility was apparently selective. Regional myocardial performance of ischaemic myocardium was increased significantly relative to nonischaemic. The selectivity of inotropic action was not mimicked by glucose-insulin-potassium. It is concluded that the selectivity is multifactoral and that the inotropic, vasodilatory and metabolic actions of the nucleoside contribute to the apparent selectivity.

The protective action of inosine on isolated arteries in hypoxia.

1 The pressor responses to injected noradrenaline (NA) of isolated perfused femoral or renal arteries of the rabbit were studied.2 Vascular smooth muscle is relatively resistant to hypoxia. A combination of hypoxia and dinitrophenol (DNP) respiratory uncoupling was necessary to abolish the pressor response to NA. Loss of the pressor response was assumed to result from decreased capacity of arteries to form adenosine 5'-triphosphate (ATP). Reperfusion of the hypoxic arteries with oxygenated medium resulted in recovery of the pressor response to NA.3 Inclusion of inosine (10 mM) in the hypoxic perfusion medium increased significantly the rate and extent of post-hypoxic recovery of the pressor response to NA.4 Whereas the presence of inosine in the hypoxic perfusion medium aided post-hypoxic recovery, inosine had no direct action on the pressor dose response to NA. Therefore, the action of inosine was protective as opposed to direct.5 The protective action of inosine did not involve potentiation of NA binding to NA-adrenoceptor sites (the equilibrium coefficient, K(eq) for NA-receptor interaction was unaltered by hypoxia and/or inosine).6 The results are discussed in terms of a presumptive mechanism whereby inosine is believed to act by maintaining intracellular adenine nucleotide concentrations in hypoxia.

Action of purine nucleosides on the release of intracellular enzymes from rat lymphocytes.

Rat lymphocytes incubated under hypoxic conditions in vitro show a time-dependent release of intracellular enzymes. As reported previously, enzyme release (lactate dehydrogenase) is decreased by metabolite, notably ATP and glucose, that contribute towards lymphocyte energy metabolism. The action of purine nucleosides in relation to enzyme release was investigated. Inosine was shown to decrease significantly lactate dehydrogenase release, whereas adenosine exerted a supportive action only at concentrations less than 0.5 mmol/l. Inosine decreased enzyme efflux maximally at concentrations of at least 2--3 mmol/l. The mechanism of inosine action was deduced to be primarily ribose 5-phosphate formation and its subsequent metabolism by energy-yielding pathways. Inosine was presumed also to enter the purine 'salvage pathway' and thereby maintain intracellular adenine nucleotide pools.